The present invention relates to an .alpha.-substituted carbonyl compound and a process for the preparation of the same.
More particularly, the present invention relates to a process for the preparation of a ketone which is substituted with an aryl or heteroaryl group at the .alpha.-position, a novel .alpha.-azo ester having an azo group at the .alpha.-position and a process for the preparation thereof, and a novel .alpha.-hydrazono ester having a hydrazono group at the .alpha.-position and a process for the preparation thereof.
A ketone which is substituted with an aryl or heteroaryl group at the .alpha.-position is important as an intermediate for the synthesis of various pharmaceuticals or agricultural chemicals.
Up to this time, the introduction of an aryl group into the .alpha.-position of a ketone has been carried out by, for example, a method which comprises reacting a silyl enol ether of .alpha.-haloketone with an aryl copper or aryl nickel, a method which comprises reacting a potassium enolate of a ketone with a halogenated aryl compound under irradiation with light, a method which comprises reacting a sulfonylazoolefin with an aryl copper, a method which comprises reacting an .alpha.-haloketone with phenylborane, a method which comprises reacting hexadienllium iron with a silyl enol ether, a method which comprises reacting an enol ester of a ketone with phenyl mercury in the presence of a palladium catalyst or a method which comprises reacting a vinyl thio ether with bromobenzene in the presence of a palladium catalyst.
However, these methods have some disadvantages in, for example, that the yield is low, that the raw material is difficultly available or that the method itself lacks generality.
Recently, a method which comprises reacting a tin enolate of a ketone produced in situ with an aryl bromide in the presence of a palladium catalyst has been found. However, this method has disadvantages in that expensive reagents such as a palladium catalyst or a tin compound are required, that the separation of the product and the recovery of the palladium catalyst and residual tin need complicated operations and that the yield is not always satisfactory.
Under these circumstances, the inventors of the present invention have investigated how to introduce an aryl or heteroaryl group into the .alpha.-position of a ketone under mild conditions in a high yield and surprisingly have found that a diazonium salt reacted with a silyl enol ether to gives a ketone which is substituted with an aryl or heteroaryl group at the. .alpha.-position along with the release of nitrogen molecule. The present invention has been accomplished on the basis of this finding.
Up to this time, the reaction between a diazonium salt and a nucleophilic reagent (for example, Grignard reagent, alkyl enol ether or lithium enolate) has been thought to give an azo or hydrazono compound as a product without the release of nitrogen molecule. Consequently, the process for the preparation of a ketone which is substituted with an aryl or heteroaryl group at the .alpha.-position according to the present invention is a novel one which can not be expected from the prior art.
The .alpha.-azo ester and .alpha.-hydrazono ester according to the present invention are each useful as an intermediate for the synthesis of an .alpha.-amino acid.
.alpha.-amino acids and their derivatives are important chemicals which are now used in sweeteners, seasoning, food additives, pharmaceuticals, agricultural chemicals, surfactants or the like as such or as a raw material and the demand for which is expected to increase with the development of biotechnology.
Although some .alpha.-amino acids can be prepared by a fermentation method using a microbe, the kind of amino acids which can be thus prepared are limited and not all amino acids can be obtained by fermentation.
Although the Strecker process using an aldehyde containing one less carbon atom is industrially employed as an organic synthesis method for an amino acid, this method requires hydrogen cyanide which is highly toxic and becomes more expensive with a decrease in the amount of hydrogen cyanide generated as a by-product in the Sohio process due to improvements in this method.
Alternatively, the Wakamatsu process which comprises the carbonylation between an amide and an aldehyde is known. But this process requires conditions of high temperature and high pressure. Further, the aldehyde to be used in the Strecker or Wakamatsu process is not always easy to obtain. Furthermore, a reductive amination method of an .alpha.-keto acid is known but no industrially advantageous methods for preparing an .alpha.-keto acid have been developed. In addition to these methods, a method which comprises aminating a carboxylic ester at the .alpha.-position is also known. According to this method, a nitrogen atom is introduced into the .alpha.-position with ammonia, phthalimide, succinimide, sodium azide or the like, after haloqenation of the ester at the .alpha.-position. However, this method has disadvantages in that the yield is not always high and that a relatively high temperature is required in the nucleophilic replacement step of a halogenated ester. As described above, methods of the prior art for the preparation of an .alpha.-amino acid or its intermediate have each disadvantages.
In view of these facts, the inventors of the present invention have investigated how to introduce an amino group or a functional group which can be converted into an amino group into the .alpha.-position of an ester and have found that a diazonium salt can be easily reacted with a ketene silyl acetal, which can be easily prepared from an ester, while releasing no nitrogen molecule, to give an azo compound or a hydrazo compound as a product. The present invention which relates to a novel .alpha.-azo ester or .alpha.-hydrazono ester or a process for the preparation thereof has been accomplished on the basis of this finding.
Up to this time, it has been thought that the reaction of a lithium enolate of an ester with a diazonium salt gives an .alpha.-azo compound and an .alpha.-hydrazono ester only in a very low yield. Consequently, the above finding can not be expected at all.